The proposed research will examine, in rats, the relationship between neurological change in the hippocampal formation which is associated with senescence, and the accompanying decline of spatial learning-memory performance. Three main areas of neurophysiological study will be covered: synaptic transmission and its modification through experience; postsynaptic integration and electrical excitability; and analysis of single unit activity in the intact freely moving animal. The methods will involve extra- and intracellular stimulation and recording in the in vitro hippocampal slice and extracellular techniques in both the acute (anesthetized) and chronically prepared (unrestrained) animal. Behavioral tests of spatial perception and memory (known to require an intact hippocampus for their proper performance) will be carried out in conjunction with some of the neurophysiological experiments. An RCDA would provide the essential training and time for additional neurochemical and neuropharmacological studies to be carried out in conjunction with the above program. Specifically, the extended project will examine the effects of aging on neuronal sensitivity to amino acids which are putative transmitters in the major pathway studied above (perforant path - fascia dentata) and its associated inhibitory interneurons. These studies would involve microiontophoresis and micropressure injections of these substances onto single neurons, both in vivo and in vitro. A second goal will be a search for the underlying biochemical basis of the decline in ability of older animals to retain stimulus-induced long-term enhancement of perforant path synapses. This investigation will primarily involve an examination of the effects of enhancing stimulation on protein phosphorylation in fascia dentata. And finally a number of pharmacological agents will be tested for their effectiveness in alleviating certain of the neurophysiological changes found normally to accompany advanced age. The long-term goal of this project is a more complete understanding of the biological basis for the deterioration of cognitive function known to occur in the elderly; a prerequisite for development of effective therapeutic measures.